crossing96/oncoscreening huggingface dataset:
Interaction between polymorphisms of DNA repair genes significantly modulated bladder cancer risk.	DNA repair is a primary defense mechanism against damage caused by exogenous and endogenous sources. We examined the associations between bladder cancer and 7 polymorphisms from 5 genes involved in the maintenance of genetic stability (MMR: MLH1-93G>A; BER: XRCC1--77T>C and Arg399Gln; NER:XPC Lys939Gln and PAT +/-; DSBR:ATM G5557A and XRCC7 G6721T) in 302 incident bladder cancer cases and 311 hospital controls. Genotyping was done using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The homozygous variant of XRCC7 G6721T (Odds Ratio [OR]: 2.36; 95% Confidence Interval [CI]: 1.13-4.92) was associated with increased bladder cancer risk. In an analysis of combined genotypes, the combination of XRCC1Arg399Gln (Gln allele) with XRCC1-77 T/T led to an increase in risk (OR: 1.61; 95% CI: 1.10-2.36). Moreover, when the XPCLys939Gln (Gln allele) (nucleotide excision repair [NER]) was present together with XRCC7 (T allele) (double strand break repair [DSBR]), the bladder cancer risk dramatically increased (OR: 4.42; 95% CI: 1.23-15.87). Our results suggest that there are multigenic variations in the DNA repair pathway involved in bladder cancer susceptibility, despite the existence of ethnic group differences.	bladder
Impact of smoking and smoking cessation on oncologic outcomes in primary non-muscle-invasive bladder cancer.	BACKGROUND: Cigarette smoking is the best-established risk factor for urothelial carcinoma (UC) development, but the impact on oncologic outcomes remains poorly understood. OBJECTIVE: To analyse the effects of smoking status, cumulative exposure, and time from smoking cessation on the prognosis of patients with primary non-muscle-invasive bladder cancer (NMIBC). DESIGN, SETTING, AND PARTICIPANTS: We collected smoking data from 2043 patients with primary NMIBC. Smoking variables included smoking status, average number of cigarettes smoked per day (CPD), duration in years, and time since smoking cessation. Lifetime cumulative smoking exposure was categorised as light short term (≤ 19 CPD, ≤ 19.9 yr), light long term (≤ 19 CPD, ≥ 20 yr), heavy short term (≥ 20 CPD, ≤ 19.9 yr) and heavy long term (≥ 20 CPD, ≥ 20 yr). The median follow-up in this retrospective study was 49 mo. INTERVENTIONS: Transurethral resection of the bladder with or without intravesical instillation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on outcomes. RESULTS AND LIMITATIONS: There was no difference in clinicopathologic factors among never (24%), former (47%), and current smokers (29%). Smoking status was associated with the cumulative incidence of disease progression in multivariable analysis (p=0.003); current smokers had the highest cumulative incidences. Among current and former smokers, cumulative smoking exposure was associated with disease recurrence (p<0.001), progression (p<0.001), and overall survival (p<0.001) in multivariable analyses that adjusted for the effects of standard clinicopathologic factors and smoking status; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation >10 yr reduced the risk of disease recurrence (hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.52-0.84; p<0.001) and progression (HR: 0.42; 95% CI, 0.22-0.83; p=0.036) in multivariable analyses. The study is limited by its retrospective nature. CONCLUSIONS: Smoking status and a higher cumulative smoking exposure are associated with worse prognosis in patients with NMIBC. Smoking cessation >10 yr abrogates this detrimental effect. These findings underscore the need for integrated smoking cessation and prevention programmes in the management of NMIBC patients.	bladder
Bladder wash cytology at diagnosis of Ta-T1 bladder cancer is predictive for recurrence and progression.	OBJECTIVE: To evaluate the effect of the bladder wash cytology finding at the primary diagnosis of Stage Ta-T1 urinary bladder cancer on recurrence and progression. METHODS: The clinical and pathologic characteristics of all patients with primary Stage Ta-T1 urinary bladder cancer were prospectively registered. The data were divided according to the bladder wash cytology results at diagnosis. Multivariate analyses were performed to determine the influence of bladder wash cytology on recurrence and progression. RESULTS: The analysis included 768 evaluable patients with a mean follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). High-grade malignant bladder wash cytology was predictive for recurrence and progression (P < .001 and P = .036, respectively). Other factors affecting recurrence were missing bladder wash cytology data, tumors size 16-30 mm and >30 mm, Stage T1 tumor category, and multiplicity (P = .008, P = .006, P < .001, P = .002, and P < .001, respectively). Progression was also associated with T1 tumor category, local recurrence, and primary concomitant carcinoma in situ (P < .001, P < .001, and P = .024, respectively). CONCLUSION: High-grade malignant bladder wash cytology at the primary diagnosis was predictive for recurrence and progression. This could be taken into account in designing future follow-up schedules.	bladder
Association between the evidence of human papilloma virus infection in bladder transitional cell carcinoma in men and cervical dysplasia in their spouses.	BACKGROUND: Cervical cancer is one of the most common tumors in women. One of its risk factors is direct contact with viruses, in particular human papillomavirus (HPV). Recent studies have shown a prevalence of 2%-35% for HPV in cases with bladder cancer. In addition, some malignancies of the urogenital organs in males may promote the probability of cervical cancer in their spouses.  In this study, the relationship between cervical dysplasia in women and evidence of HPV infection in tissue specimens obtained from their spouses' bladders has been investigated. METHODS: This cross-sectional study was conducted on 82 male patients with bladder tumors and their spouses between February 2004 and February 2007 in Tehran. We gathered data related to the histopathology of the transitional cell carcinoma (TCC) in men and Pap smear tests of their spouses. Tissue specimens of patients with bladder TCC were analyzed for HPV infection using polymerase chain reaction (PCR). HPV-positive specimens were tested for subtypes 16 and 18. RESULTS: In 24 (29.3%) men, bladder tumor samples were positive for HPV infection. Of these, we found HPV-18 infection in 9 (37.5%), while 3 (12.5%) were infected with HPV-16. In the spouses of those men with HPV-infected bladder tumors, 4 (4.9%) cases had cellular dysplasia noted on their Pap smear tests. We found no dysplasia in those women whose husbands had bladder TCC, but no HPV infection (P = 0.006). CONCLUSION: It is possible to decrease the incidence of bladder TCC in men and cervical cancer in women through public education regarding the methods of transmission and avoidance of risky sexual behaviors.	bladder
Epidermal growth factor induces bladder cancer cell proliferation through activation of the androgen receptor.	Androgen receptor (AR) signals have been suggested to contribute to bladder tumorigenesis and cancer progression. Activation of epidermal growth factor receptor (EGFR) also leads to stimulation of bladder tumor growth. However, crosstalk between AR and EGFR pathways in bladder cancer remains uncharacterized. We have recently shown that androgens activate the EGFR pathway in bladder cancer cells. The purpose of this study was to investigate the effects of EGF on AR activity in bladder cancer. EGF increased AR transcriptional activity by 1.2-, 1.9- and 2.0-fold in UMUC3, 5637-AR and J82-AR cell lines, respectively, over mock treatment and a specific EGFR inhibitor, PD168393, antagonized the EGF effect. Combined treatment of EGF and dihydrotestosterone (DHT) further induced AR transactivation while an AR antagonist, hydroxyflutamide (HF), abolished the effect of not only DHT but also EGF. In growth assays, EGF alone/DHT alone/EGF+DHT increased cell numbers by 16/12/19%, 6/14/18% and 30/12/38% in UMUC3-control-shRNA, 5637-AR and J82-AR, respectively, whereas the effects of EGF were marginal or less significant in UMUC3-AR-shRNA (8%) or AR-negative 5637-V (<1%) and J82-V (17%) cells. HF treatment at least partially counteracted the EGF effect on the growth of AR-positive cells. Western blotting demonstrated that EGF, especially in the presence of DHT, upregulated the expression of the p160 coactivator TIF2 and HF again blocked this stimulation. Co-immunoprecipitation revealed the association between AR and estrogen receptor (ER)-β or Src in UMUC3 cells and stronger associations with EGF treatment, implying the involvement of the AR/ER/Src complex in EGF-increased AR transactivation and cell growth. Current results, thus, suggest that EGF promotes bladder cancer cell proliferation via modulation of AR signals. Taken together with our previous findings, crosstalk between EGFR and AR pathways can play an important role in the progression of bladder cancer.	bladder
Inhibition of STAT signalling in bladder cancer by diindolylmethane: relevance to cell adhesion, migration and proliferation.	Effective treatments to prevent recurrence or progression of non-muscle-invasive bladder cancer, or to inhibit metastasis of muscle-invasive forms of the disease, would deliver significant patient benefit. Here the involvement of STAT signalling and the chemopreventive potential of diindolylmethane (DIM) in human bladder cancer were investigated. Muscle-invasive bladder cancer tissues were characterised by nuclear expression of phosphorylated STAT1, 3 and 5. In E-cadherin positive tumour cell lines (RT112, RT4, HT1376), STAT5 was constitutively phosphorylated, while E-cadherin negative lines (J82, T24, UMUC3) contained phosphoSTAT3. Knockdown of STAT3 induced G₀/G₁ arrest and inhibited adhesion in J82 cells. Knockdown of STAT1inhibited migration in J82 and RT112 lines. No significant increase in apoptosis was observed. In response to the Janus kinase inhibitor, AG490, RT112 and J82 cells initially underwent G₀/G₁ arrest, with RT112 cells subsequently exhibiting S phase arrest. Phosphorylation of STAT1(Tyr701), STAT3(Tyr705) and (Ser727) and STAT5(Tyr694) was inhibited by DIM, as was adhesion of J82 cells to collagen, an effect that was enhanced when STAT1 or 3 was reduced by siRNA. However, over-expression of STAT3C partially rescued the DIM inhibitory effect on collagen-mediated adhesion. Migration of both lines was inhibited by DIM, while transfection of constitutively active STAT3C enhanced migration of RT112 cells. DIM induced cell cycle arrest and apoptosis in three cell lines with different degrees of radioresistance. Taken together, these results suggest that inhibition of STAT signalling and/or treatment with DIM may decrease invasiveness of bladder cancer. DIM can induce apoptosis in cell lines which are radioresistant, so in combination with radiotherapy may be useful in overcoming such resistance.	bladder
ICUD-EAU International Consultation on Bladder Cancer 2012: Chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings.	CONTEXT: We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of bladder cancer using an evidence-based strategy. OBJECTIVE: To review the data regarding chemotherapy in patients with clinically localized and metastatic bladder cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings. EVIDENCE ACQUISITION: Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: bladder cancer, urothelial cancer, metastatic, advanced, neoadjuvant, and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included. EVIDENCE SYNTHESIS: The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed. CONCLUSIONS: Cisplatin-based combination chemotherapy for advanced and metastatic bladder cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking.	bladder
Characteristics of lymph node metastases defining the outcome after radical cystectomy of urothelial bladder carcinoma.	OBJECTIVE: The aim of this study was to identify clinicopathological variables associated with the clinical outcomes of patients with lymph node metastasis-positive urothelial bladder carcinoma after radical cystectomy. METHODS: Forty-six patients who underwent radical cystectomy without preoperative chemotherapy and had histologically proven nodal metastasis were included in the study. The status of lymph nodes and primary lesion was analyzed in terms of disease-specific survival and recurrence-free survival. RESULTS: The 5-year disease-specific survival and recurrence-free survival for the 46 patients overall were 41.3 and 32.2%, respectively. Univariate analysis showed that pN status, the total number of involved lymph nodes, lymph node density and extranodal invasion were statistically significant variables predictive of disease-specific survival. Multivariate analysis revealed that the total number of involved lymph nodes, extranodal invasion and diameter of the metastatic lesion were statistically significant variables predictive of disease-specific survival. Interestingly, the diameter of metastatic lesions was inversely correlated with poorer survival. Patients with large (≥10 mm) metastatic lesions and no extranodal invasion (expansive growth) had significantly better disease-specific survival than those with multiple small (<10 mm) metastatic lesions and no extranodal invasion (highly spreading) (P=0.0156) or those with extranodal invasion (infiltrative growth) (P=0.0181). CONCLUSIONS: Our data indicate that the clinical outcome of node-positive patients is not only stratified according to the tumor burden reflected in the total number of involved lymph nodes, but also affected by tumor biology including invasiveness and potential for metastasis, which is reflected in pathological characteristics such as extranodal invasion and the diameter of metastatic lesions.	bladder
P53 Arg72Pro polymorphism and bladder cancer risk--meta-analysis evidence for a link in Asians but not Caucasians.	OBJECTIVE: Individual studies of the associations between P53 codon 72 polymorphism (rs1042522) and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship, we performed this systemic review and meta-analysis based on 15 publications. METHODS: We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. RESULTS: We found that there was no association between P53 codon 72 polymorphism and bladder cancer risk in the comparisons of Pro/ Pro vs Arg/Arg; Pro/Arg vs. Arg/Arg; Pro/Pro plus Pro/Arg vs. Arg/Arg; Arg/Arg vs. Pro/Arg plus Arg/Arg (OR=1.06 95%CI 0.81-1.39; OR=1.06 95%CI 0.83-1.36; OR=0.98 95%CI 0.78-1.23; OR=1.06 95%CI 0.84-1.32). However, a significantly increased risk of bladder cancer was found among Asians in the homozygote comparison (Pro/Pro vs. Arg/Arg, OR=1.36 95%CI 1.05-1.75, P=0.790 for heterogeneity) and the dominant model (Arg/Pro plus Pro/Pro vs. Arg/Arg, OR=1.26 95%CI 1.05-1.52, P=0.564 for heterogeneity). In contrast, no evidence of an association between bladder cancer risk and P53 genotype was observed among Caucasian population in any genetic model. When stratifying for the stage of bladder, no statistical association were found (Pro/Pro vs. Arg/Arg, OR=0.45 95%CI 0.17-1.21; Pro/Arg vs. Arg/Arg, OR=0.60 95%CI 0.28-1.27; Dominant model, OR=0.56 95%CI 0.26-1.20; Recessive model, OR=0.62 95%CI 0.35-1.08) between P53 codon 72 polymorphism and bladder cancer in all comparisons. CONCLUSIONS: Despite the limitations, the results of the present meta-analysis suggest that, in the P53 codon 72, Pro/Pro type and dominant mode might increase the susceptibility to bladder cancer in Asians; and there are no association between genotype distribution and the stage of bladder cancer.	bladder
A novel molecular grading model: combination of Ki67 and VEGF in predicting tumor recurrence and progression in non-invasive urothelial bladder cancer.	PURPOSE: To assess efficacy of Ki67 combined with VEGF as a molecular grading model to predict outcomes with non-muscle invasive bladder cancer (NMIBC). MATERIALS: 72 NMIBC patients who underwent transurethral resection (TUR) followed by routine intravesical instillations were retrospectively analyzed in this study. Univariate and multivariate analyses were performed to confirm the prognostic values of the Ki67 labeling index (LI) and VEGF scoring for tumor recurrence and progression. RESULTS: The novel molecular grading model for NMIBC contained three molecular grades including mG1 (Ki67 LI≤25%, VEGF scoring≤8), mG2 (Ki67 LI>25%, VEGF scoring≤8; or Ki67 LI≤25%, VEGF scoring>8), and mG3 (Ki67 LI>25%, VEGF scoring>8), which can indicate favorable, intermediate and poor prognosis, respectively. CONCLUSIONS: The described novel molecular grading model utilizing Ki67 LI and VEGF scoring is helpful to effectively and accurately predict outcomes and optimize personal therapy.	bladder
Methotrexate-paclitaxel-epirubicin-carboplatin as second-line chemotherapy in patients with metastatic transitional cell carcinoma of the bladder pretreated with cisplatin-gemcitabine: a phase II study.	AIMS: To assess the efficacy and toxicity of methotrexate-paclitaxel-epirubicin-carboplatin combination as second-line chemotherapy in patients with metastatic transitional cell carcinoma (TCC) of the bladder pretreated with cisplatin-gemcitabine. METHODS: In this prospective phase II study, patients with metastatic TCC of the bladder pretreated with first-line cisplatin-gemcitabine received on progression paclitaxel 175 mg/m(2) i.v. and carboplatin (area under curve of 5) on day 1, and methotrexate 40 mg/m(2) and epirubicin 40 mg/m(2) on day 15. The whole course was repeated every 28 days. The end-points included clinical tumor response, treatment toxicity, quality of life and survival. RESULTS: A total of 40, predominantly male, patients were enrolled (median age 62 years [range 46-69]). Efficacy and survival were assessed in 38 patients only, as two patients refused treatment after the first cycle. Grade 3 neutropenia was the commonest acute severe toxicity (12/40 patients; 30%). The overall response rate was 39% (15/38 patients). The median follow up was 14 months (range 3-45). The median progression-free and overall survival were 12 and 12.5 months, respectively. The 1-year progression-free and overall survival were 24 and 35%, respectively. CONCLUSION: Methotrexate-paclitaxel-epirubicin-carboplatin combination as second-line chemotherapy in patients with metastatic TCC of the bladder results in a modest response rate with acceptable toxicity.	bladder
Role of C-reactive protein in urological cancers: a useful biomarker for predicting outcomes.	Based on increasing evidence of the association between cancer-related inflammation and the progression of cancer, the external symptoms of systemic inflammatory response has been shown to be an indicator for the prognosis of many malignancies, including urological cancers. C-reactive protein, a representative acute-phase reactant, is a significant and sensitive inflammatory marker that can be objectively measured using reliable assays in clinical practice worldwide. C-reactive protein has been shown to be significant in the prediction of outcomes of urological cancers. The elevation of C-reactive protein levels, which indicate the presence of cancer-associated systemic inflammatory response, is linked to poorer survival in patients with urological cancers, including renal cell carcinoma, upper urinary tract and bladder cancers, and prostate cancer. With this strong prognostic ability, C-reactive protein can be incorporated into prognostic models and will make them simpler and improve their predictive accuracy. Furthermore, the longitudinal change of C-reactive protein level, C-reactive protein kinetics, provides additional information on patient survival outcomes. As such, C-reactive protein can be used to monitor treatment efficacy and disease course using serial measurements. In testicular cancer, C-reactive protein is associated with a risk of late complications, such as cardiovascular disease, and with the development of second non-germ-cell cancer. Taken together, these findings show that C-reactive protein can act as an important biomarker for urological cancers. This review discusses the importance of C-reactive protein as a prognostic biomarker in urological cancers on the basis of the currently available evidence.	bladder
The Chinese herb isolate isorhapontigenin induces apoptosis in human cancer cells by down-regulating overexpression of antiapoptotic protein XIAP.	Although the Chinese herb Gnetum cleistostachyum has been used as a remedy for cancers for hundred years, the active compounds and molecular mechanisms underlying its anti-cancer activity have not been explored. Recently a new derivative of stilbene compound, isorhapontigenin (ISO), was isolated from this Chinese herb. In the present study, we examined the potential of ISO in anti-cancer activity and the mechanisms involved in human cancer cell lines. We found that ISO exhibited significant inhibitory effects on human bladder cancer cell growth that was accompanied by marked apoptotic induction as well as down-regulation of the X-linked inhibitor of apoptosis protein (XIAP). Further studies have shown that ISO down-regulation of XIAP protein expression was only observed in endogenous XIAP, but not in constitutionally exogenously expressed XIAP in the same cells, excluding the possibility of ISO regulating XIAP expression at the level of protein degradation. We also identified that ISO down-regulated XIAP gene transcription via inhibition of Sp1 transactivation. There was no significant effect of ISO on apoptosis and colony formation of cells transfected with exogenous HA-tagged XIAP. Collectively, current studies, for the first time to the best of our knowledge, identify ISO as a major active compound for the anti-cancer activity of G. cleistostachyum by down-regulation of XIAP expression and induction of apoptosis through specific targeting of a SP1 pathway, and cast new light on the treatment of the cancer patients with XIAP overexpression.	bladder